Penicillins – Cell Wall Synthesis Inhibitors (Antibiotics)

Antibiotics are an indispensable part of modern medicine. Many infectious diseases caused by bacteria are fatal without antibiotic treatment. Therefore, the empirical use of antibiotics is the basic component of many therapies. However, due to increasing resistance and the increased incidence of long underestimated problematic bacteria, such as Acinetobacter baumanii complex, every medical student and practitioner should know the common antibiotics, their indications, and frequent side effects.

00:00
Let's start off with
the penicillins.
00:03
So remember that penicillins
are active on the cell wall.
00:07
Now the cell walls
you can see them here.
00:10
They have sites that are
amenable to transpeptidation.
00:14
This allows cross-linking of
the components of the wall.
00:18
And when you have cross-linking
you have a stronger wall.
00:22
Now cross-linking is created
or facilitated by proteinsthat act on those peptidoglycans of the cell walland links them together.
00:31
Much like a zipper does.
00:32
Penicillins have a beta
lactam ring that bindsto that protein.
00:38
And for this reason the proteins
are called penicillin bindingproteins.
00:43
So penicillin binding protein
is where the penicillin is goingto be active.
00:48
Now if you inhibit
the penicillin binding protein,autocatalysis of the cell wall
will occur and the cell wallwill break down.
00:57
Now, the bacteria have
developed defense mechanismsagainst the penicillins.
01:04
So some bacteria have
beta lactamase enzymes.
01:08
They're also called
penicillinases in other partsof the world.
01:12
Now these beta lactamase break
down that beta lactam ring.
01:16
This is the mechanism of
most types of resistance.
01:19
And they're countered by
the inhibitors of these enzymes.
01:23
So clavulanic acid is an
agent that inhibitsthe beta lactamase.
01:28
Now we use that in
combination with amoxicillin.
01:31
And we sell it as a
amoxicillin clavulanate.
01:34
Sub lactam is another beta
lactamase and we sometimescombine that particular agent
with ampicillin and we sellampicillin sublactam.
01:45
And tazobactam is the third
one and for example,they'll combine with
piperacillin as peptazo.
01:54
Now there are other mechanisms
of resistance that bacteriawill have against penicillin.
02:00
Sometimes there is actually
a structural change inthe penicillin binding protein
which renders immunityor resistance to penicillins.
02:08
This is actually the mechanism
of methicillin resistance.
02:12
And it's become a real problem in our hospitals.
02:15
Sometimes there's actually
a change in the porin structureof the outer wall.
02:20
So for example resistance
of pseudomonas to penicillinsis a great example.
02:25
The penicillin isn't able
to penetratebecause there is a change
in the porin.
02:30
Now we'll talk about some
narrow spectrum penicillinsthat are out there.
02:36
Methicillin, naficillin
and oxacillinare narrow spectrum agents.
02:42
They are not used much anymore.
02:43
I remember when we started
medicine,we used to use methicillin
all the time.
02:48
Methicillin resistant
staphylococcus is essentiallytaken methicillin of the table
in terms of our choice.
02:54
Because these MRSA's are
resistant to all penicillins.
02:59
Methicillin is also linked
to interstitial nephritits.
03:04
Naficillin is associated
with neutropenia.
03:07
So these agents are
falling out of favor.
03:09
But they still do show up on
our susceptibility charts.
03:12
Now ampicillin and amoxicillin,
you probably quitefamiliar with.
03:18
In fact I would bet that some
of you have been on thesemedications yourselves.
03:22
These are wide spectrum agents.
03:24
But they are still susceptible
to beta lactamases.
03:28
They are enhanced when
combined with clavulanate.
03:31
And enterococcal infections,
ampicillin is complementarywith aminoglycosides.
03:38
So in enterococcal infections,
we'll often use combinationslike ampicillin and gentamicin.
03:43
Because they work
very well together.
03:45
That's called bacterial synergy.
03:47
And I'm going to mention
it again when I talk aboutgentamicin.
03:51
Piperacillin and ticarcillin
are stronger agents.
03:56
These are very strong
agents against gram negativeorganisms.
04:01
And once again they are
very complimentarywith aminoglycosides.
04:05
So piperacillin for example will
be combined with tobramicinto give a very strong gram
negative treatment.
04:11
Once again these drugs
are susceptibleto the penicillinases.
04:16
So we often combine drugs like
piperacillin with tazobactamto limit the resistance.

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